tbuckley/cabot-search huggingface dataset:
Identification of proteinase 3 autoreactive CD4+T cells and their T-cell receptor repertoires in antineutrophil cytoplasmic antibody–associated vasculitis
Authors: Ravi Kumar Sharma, Niyaz Yoosuf, Marcelo Afonso, Andrea Scheffschick, Aune Avik, Alice Bartoletti, Begum Horuluoglu, Juan Sebastian Diaz Boada, Sanjay Kumar Boddul, Asta Dögg Jonasdottir, Björn Lövström, Hanna Brauner, Bruno Raposo, Karine Chemin, Annette Bruchfeld, Iva Gunnarsson, Vivianne Malmström
Journal: Kidney International (2023)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease involving autoreactivity to proteinase 3 (PR3) as demonstrated by presence of ANCAs. While autoantibodies are screened for diagnosis, autoreactive T cells and their features are less well-studied. Here, we investigated PR3-specific CD4+T cell responses and features of autoreactive T cells in patients with PR3-AAV, using a cohort of 72 patients with either active or inactive disease. Autoreactive PR3-specific CD4+T cells producing interferon γ in response to protein stimulation were found to express the G-protein coupled receptor 56 (GPR56), a cell surface marker that distinguishes T cells with cytotoxic capacity. GPR56+CD4+T cells were significantly more prominent in the blood of patients with inactive as compared to active disease, suggesting that these cells were affected by immunosuppression and/or that they migrated from the circulation to sites of organ involvement. Indeed, GPR56+CD4+T cells were identified in T-cell infiltrates of affected kidneys and an association with immunosuppressive therapy was found. Moreover, distinct TCR gene segment usage and shared (public) T cell clones were found for the PR3-reactive TCRs. Shared T cell clones were found in different patients with AAV carrying the disease-associated HLA-DP allele, demonstrating convergence of the autoreactive T cell repertoire. Thus, we identified a CD4+T cell signature in blood and in affected kidneys that display PR3 autoreactivity and associates with T cell cytotoxicity. Our data provide a basis for novel rationales for both immune monitoring and future therapeutic intervention in PR3-AAV.
Mitochondrial micropeptide MOXI promotes fibrotic gene transcription by translocation to the nucleus and bridging N-acetyltransferase 14 with transcription factor c-Jun
Authors: Jinhua Li, Xinli Qu, Chengnong Guan, Ning Luo, Huiting Chen, Andy Li, Hongjie Zhuang, Jiayi Yang, Hui Diao, Shuhan Zeng, Qing Wang, Jinjin Fan, Mengjie Jiang, Xiaoyan Bai, Zhiming Ye, Xiaoyun Jiang, Wei Chen, David J. Nikolic-Paterson, Xueqing Yu
Journal: Kidney International (2023)
The combined effect of metformin and mirabegron on diet‐induced obesity
Authors: Xin‐Yuan Zhao, Ying Liu, Xuan Zhang, Ben‐Chi Zhao, George Burley, Zhi‐Can Yang, Yi Luo, An‐Qi Li, Ruo‐Xin Zhang, Zhi‐Ying Liu, Yan‐Chuan Shi, Qiao‐Ping Wang
Journal: MedComm (2023)

Anti-obesity medications act by suppressing energy intake (EI), promoting energy expenditure (EE), or both. Metformin (Met) and mirabegron (Mir) cause weight loss by targeting EI and EE, respectively. However, anti-obesity effects during concurrent use of both have yet to be explored. In this study, we investigated the anti-obesity effects, metabolic benefits, and underlying mechanisms of Met/Mir combination therapy in two clinically relevant contexts: the prevention model and the treatment model. In the prevention model, Met/Mir caused further 12% and 14% reductions in body weight (BW) gain induced by a high-fat diet compared to Met or Mir alone, respectively. In the treatment model, Met/Mir additively promoted 17% BW loss in diet-induced obese mice, which was 13% and 6% greater than Met and Mir alone, respectively. Additionally, Met/Mir improved glucose tolerance and insulin sensitivity. These benefits of Met/Mir were associated with increased EE, activated brown adipose tissue thermogenesis, and white adipose tissue browning. Significantly, Met/Mir did not cause cardiovascular dysfunction in either model. Together, the combination of Met and Mir could be a promising approach for the prevention and treatment of obesity by targeting both EI and EE simultaneously.
‘Small Data’ for big insights in ecology
Authors: Lindsay C. Todman, Alex Bush, Amelia S.C. Hood
Journal: Trends in Ecology & Evolution (2023)

Big Data science has significantly furthered our understanding of complex systems by harnessing large volumes of data, generated at high velocity and in great variety. However, there is a risk that Big Data collection is prioritised to the detriment of 'Small Data' (data with few observations). This poses a particular risk to ecology where Small Data abounds. Machine learning experts are increasingly looking to Small Data to drive the next generation of innovation, leading to development in methods for Small Data such as transfer learning, knowledge graphs, and synthetic data. Meanwhile, meta-analysis and causal reasoning approaches are evolving to provide new insights from Small Data. These advances should add value to high-quality Small Data catalysing future insights for ecology.
Stiffness-tuned and ROS-sensitive hydrogel incorporating complement C5a receptor antagonist modulates antibacterial activity of macrophages for periodontitis treatment
Authors: Ziqi Gan, Zecong Xiao, Zhen Zhang, Yang Li, Chao Liu, Xin Chen, Yuanbo Liu, Dongle Wu, Chufeng Liu, Xintao Shuai, Yang Cao
Journal: Bioactive Materials (2023)

Periodontitis is admittedly a microbe-driven intractable infectious disease, in which Porphyromonas gingivalis (Pg) plays a keystone role. Pg can selectively impair the antimicrobial responses of periodontal resident macrophages including their phagocytic and bactericidal activity without interfering their proinflammatory activity, which leads to microflora disturbance, destructive periodontal inflammation and alveolar bone loss eventually. Here, an injectable ROS-sensitive hydrogel is developed for releasing active bone marrow-derived macrophages (named ex-situ macrophages hereafter) and a complement C5a receptor antagonist (C5A) to the gingival crevice. Through appropriately tuning the hydrogel stiffness, the phagocytic activity of these macrophages is greatly enhanced, reaching an optimal performance at the elastic modulus of 106 kPa. Meanwhile, C5A avoids undesired C5a receptor activation by Pg to ensure the bacterial killing activity of both the ex-situ and in-situ macrophages. Besides, the ROS-sensitive hydrogels show another distinct feature of decreasing the ROS level in periodontal niche, which contributes to the alleviated periodontal inflammation and attenuated bone loss as well. This study highlights the potential of utilizing hydrogels with tailored biomechanical properties to remodel the functions of therapeutic cells, which is expected to find wide applications even beyond periodontitis treatment.
Corrigendum to “Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer” [Pharmacology &amp; Therapeutics 239 (2022) 108296]
Authors: Xinlin Liu, Junwen Deng, Yang Yuan, Wujun Chen, Wenshe Sun, Yanhong Wang, Haiming Huang, Bing Liang, Tao Ming, Jialian Wen, Binghuan Huang, Dongming Xing
Journal: Pharmacology & Therapeutics (2023)
Concomitant Venetoclax and Imatinib for Comanaging Chronic Lymphocytic Leukemia and Chronic Myeloid Leukemia: A Case Report
Authors: Eugene R. Przespolewski, Jeffrey Baron, Farshid Kashef, Kai Fu, Sheila N. Jani Sait, Francisco Hernandez-Ilizaliturri, James Thompson
Journal: Journal of the National Comprehensive Cancer Network (2023)

Patients with synchronous malignancies can be problematic to diagnose and manage because workup and therapeutic targeting for each individual malignancy must be coordinated carefully. This report presents a patient with concurrent chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) managed with concomitant venetoclax and imatinib. Because imatinib is a moderate cytochrome P450 3A4 inhibitor, close monitoring is required when using with a substrate of 3A4 such as venetoclax. Although the target dose of venetoclax is 400 mg, it was capped at 100 mg due to the interaction. Despite the interaction and possible enhancement of toxicities, the patient has tolerated therapy well, and both diseases have responded to this novel approach. In addition, because aberrant BCL-2 activity has been implicated in CML, the use of venetoclax may contribute to success in the management of this patient's CML. This case report represents the safe concomitant use of venetoclax and imatinib in a patient with synchronous CML and CLL.
Effect of Yoga and Mediational Influence of Fatigue on Walking, Physical Activity, and Quality of Life Among Cancer Survivors
Authors: Po-Ju Lin, Brian J. Altman, Nikesha J. Gilmore, Kah Poh Loh, Richard F. Dunne, Javier Bautista, Chunkit Fung, Michelle C. Janelsins, Luke J. Peppone, Marianne K. Melnik, Kim O. Gococo, Michael J. Messino, Karen M. Mustian
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Cancer-related fatigue (CRF) negatively affects survivors’ walking, engagement in physical activity (PA), and quality of life (QoL). Yoga is an effective therapy for treating CRF; however, evidence from large clinical trials regarding how reducing CRF through yoga influences CRF’s interference with survivors’ walking, engagement in PA, and QoL is not available. We examined the effects of yoga and the mediational influence of CRF on CRF’s interference with walking, PA, and QoL among cancer survivors in a multicenter phase III randomized controlled trial. Patients and Methods: Cancer survivors (n=410) with insomnia 2 to 24 months posttreatment were randomized to a 4-week yoga intervention—Yoga for Cancer Survivors (YOCAS)—or standard care. A symptom inventory was used to assess how much CRF interfered with survivors’ walking, PA, and QoL. The Multidimensional Fatigue Symptom Inventory-Short Form was used to assess CRF. Two-tailed t tests and analyses of covariance were used to examine within-group and between-group differences. Path analysis was used to evaluate mediational relationships between CRF and changes in CRF’s interference with walking, PA, and QoL among survivors. Results: Compared with standard care controls, YOCAS participants reported significant improvements in CRF’s interference with walking, PA, and QoL at postintervention (all effect size = −0.33; all P ≤.05). Improvements in CRF resulting from yoga accounted for significant proportions of the improvements in walking (44%), PA (53%), and QoL (45%; all P ≤.05). Conclusions: A significant proportion (44%–53%) of the YOCAS effect on CRF’s interference with walking, PA, and QoL was due to improvements in CRF among cancer survivors. Yoga should be introduced and included as a treatment option for survivors experiencing fatigue. By reducing fatigue, survivors further improve their walking, engagement in PA, and QoL.
Advancing More Equitable Care Through the Development of a Health Equity Report Card
Authors: Alyssa A. Schatz, Shonta Chambers, Gretchen C. Wartman, Lisa A. Lacasse, Crystal S. Denlinger, Kristen M. Hobbs, Lindsey Bandini, Robert W. Carlson, Robert A. Winn
Journal: Journal of the National Comprehensive Cancer Network (2023)

The root causes of racial disparities in access to optimal cancer care and related cancer outcomes are complex, multifactorial, and not rooted in biology. Contributing factors to racial disparities in care delivery include implicit and explicit bias, lack of representation of people of color in the oncology care and research workforce, and homogenous research participants that are not representative of the larger community. Systemic and structural barriers include policies leading to lack of insurance and underinsurance, costs of cancer treatment and associated ancillary costs of care, disparate access to clinical trials, and social determinants of health, including exposure to environmental hazards, access to housing, childcare, and economic injustices. To address these issues, ACS CAN, NCCN, and NMQF convened the Elevating Cancer Equity (ECE) initiative. The ECE Working Group developed the Health Equity Report Card (HERC). In this manuscript, we describe the process taken by the ECE Working Group to develop the HERC recommendations, the strategies employed by NCCN to develop an implementation plan and scoring methodology for the HERC, and next steps to pilot the HERC tool in practice settings.
Erratum
Journal: Journal of the National Comprehensive Cancer Network (2023)

Cabozantinib moved from "Useful in Certain Circumstances" to "Other Recommended Regimens."➤ Useful in Certain Circumstances (Biomarker directed: after prior systemic therapy): Lenvatinib/pembrolizumab (category 1) for non-MSI-high [MSI-H]/ non-MMR-deficient [dMMR] mismatch repair proficient (pMMR) tumors.Pembrolizumab for TMB-H or MSI-H/dMMRl tumors was changed from category 2A to category 1. Dostarlimab-gxly for dMMR/MSI-H tumors was changed from category 2A to category 1.
Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology
Authors: Nadeem Abu-Rustum, Catheryn Yashar, Rebecca Arend, Emma Barber, Kristin Bradley, Rebecca Brooks, Susana M. Campos, Junzo Chino, Hye Sook Chon, Christina Chu, Marta Ann Crispens, Shari Damast, Christine M. Fisher, Peter Frederick, David K. Gaffney, Robert Giuntoli, Ernest Han, Jordan Holmes, Brooke E. Howitt, Jayanthi Lea, Andrea Mariani, David Mutch, Christa Nagel, Larissa Nekhlyudov, Mirna Podoll, Ritu Salani, John Schorge, Jean Siedel, Rachel Sisodia, Pamela Soliman, Stefanie Ueda, Renata Urban, Stephanie L. Wethington, Emily Wyse, Kristine Zanotti, Nicole R. McMillian, Shaili Aggarwal
Journal: Journal of the National Comprehensive Cancer Network (2023)

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.
Molecular Profiling of Endometrial Cancer From TCGA to Clinical Practice
Authors: Amy Jamieson, Jessica N. McAlpine
Journal: Journal of the National Comprehensive Cancer Network (2023)

Molecular classification provides an objective, reproducible framework for categorization of endometrial cancers (ECs), informing prognosis and selection of therapy. Currently, the uptake of molecular classification, integration in to EC management algorithms, and enrollment in molecular subtype-specific clinical trials lags behind what it could be. Access to molecular testing is not uniform, and subsequent management (surgical, adjuvant therapy) is unacceptably variable. We are in the midst of a critical landscape change in this disease site, with increasing emphasis on the integration of molecular features in EC care that can potentially improve standard of care globally. This article summarizes the rationale for molecular classification of ECs, strategies for implementation in low and high resource settings, and actionable opportunities based on this information.
NCCN Guidelines® Insights: Hematopoietic Cell Transplantation, Version 3.2022
Authors: Ayman Saad, Alison Loren, Javier Bolaños-Meade, George Chen, Daniel Couriel, Antonio Di Stasi, Areej El-Jawahri, Hany Elmariah, Sherif Farag, Krishna Gundabolu, Jonathan Gutman, Vincent Ho, Rasmus Hoeg, Mitchell Horwitz, Joe Hsu, Adetola Kassim, Mohamed Kharfan Dabaja, John Magenau, Thomas Martin, Marco Mielcarek, Jonathan Moreira, Ryotaro Nakamura, Yago Nieto, Cameron Ninos, Caspian Oliai, Seema Patel, Brion Randolph, Mark Schroeder, Dimitrios Tzachanis, Asya Nina Varshavsky-Yanovsky, Madhuri Vusirikala, Frankie Algieri, Lenora A. Pluchino
Journal: Journal of the National Comprehensive Cancer Network (2023)

The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease—a major complication of allogeneic HCT—to enable the patient and clinician to assess management options in the context of an individual patient’s condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.
Innate immune memory in cardiometabolic disease
Authors: Harsh Bahrar, Siroon Bekkering, Rinke Stienstra, Mihai G Netea, Niels P Riksen
Journal: Cardiovascular Research (2023)

Abstract Low-grade systemic inflammation is a key pathophysiological component of atherosclerotic cardiovascular disease (CVD), and long-term activation of myeloid cells is thought to be crucial for these effects. Obesity and associated metabolic complications including hyperglycaemia and dyslipoproteinaemia can induce long-lasting inflammatory reprogramming of the innate immune cells and their bone marrow progenitors, which in turn contributes to atherosclerosis. In this review, we discuss the mechanisms through which innate immune cells undergo long-term changes in their functional, epigenetic, and metabolic characteristics upon even short-term exposure to endogenous ligands, a process also termed ‘trained immunity’. Inappropriate induction of trained immunity leads to the development of long-lasting hyperinflammatory and proatherogenic changes in monocytes and macrophages, an important factor in the development of atherosclerosis and CVDs. Knowledge of the specific immune cells and the distinct intracellular molecular pathways involved in the induction of trained immunity will reveal novel pharmacological targets that could be used to prevent or treat CVDs in the future.
Historical redlining and breast cancer treatment and survival among older women in the United States
Authors: Jean C Bikomeye, Yuhong Zhou, Emily L McGinley, Bethany Canales, Tina W F Yen, Sergey Tarima, Sara Beltrán Ponce, Kirsten M M Beyer
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Breast cancer (BC) is the most common cancer among US women, and institutional racism is a critical cause of health disparities. We investigated impacts of historical redlining on BC treatment receipt and survival in the United States. Methods Home Owners’ Loan Corporation (HOLC) boundaries were used to measure historical redlining. Eligible women in the 2010-2017 Surveillance, Epidemiology, and End Results–Medicare BC cohort were assigned a HOLC grade. The independent variable was a dichotomized HOLC grade: A and B (nonredlined) and C and D (redlined). Outcomes of receipt of various cancer treatments, all-cause mortality (ACM), and BC-specific mortality (BCSM) were analyzed using logistic or Cox models. Indirect effects by comorbidity were examined. Results Among 18 119 women, 65.7% resided in historically redlined areas (HRAs), and 32.6% were deceased at a median follow-up of 58 months. A larger proportion of deceased women resided in HRAs (34.5% vs 30.0%). Of all deceased women, 41.6% died of BC; a larger proportion resided in HRAs (43.4% vs 37.8%). Historical redlining is a statistically significant predictor of poorer survival after BC diagnosis (hazard ratio = 1.09, 95% confidence interval [CI] = 1.03 to 1.15 for ACM, and hazard ratio = 1.26, 95% CI = 1.13 to 1.41 for BCSM). Indirect effects via comorbidity were identified. Historical redlining was associated with a lower likelihood of receiving surgery (odds ratio = 0.74, 95% CI = 0.66 to 0.83, and a higher likelihood of receiving palliative care odds ratio = 1.41, 95% CI = 1.04 to 1.91). Conclusion Historical redlining is associated with differential treatment receipt and poorer survival for ACM and BCSM. Relevant stakeholders should consider historical contexts when designing and implementing equity-focused interventions to reduce BC disparities. Clinicians should advocate for healthier neighborhoods while providing care.
Bioinformatics Analysis of Mutations Sheds Light on the Evolution of Dengue NS1 Protein With Implications in the Identification of Potential Functional and Druggable Sites
Authors: Abhishek Sharma, Sudhir Krishna, Ramanathan Sowdhamini
Journal: Molecular Biology and Evolution (2023)

Abstract Non-structural protein (NS1) is a 350 amino acid long conserved protein in the dengue virus. Conservation of NS1 is expected due to its importance in dengue pathogenesis. The protein is known to exist in dimeric and hexameric states. The dimeric state is involved in its interaction with host proteins and viral replication, and the hexameric state is involved in viral invasion. In this work, we performed extensive structure and sequence analysis of NS1 protein, and uncovered the role of NS1 quaternary states in its evolution. A three-dimensional modeling of unresolved loop regions in NS1 structure is performed. “Conserved” and “Variable” regions within NS1 protein were identified from sequences obtained from patient samples and the role of compensatory mutations in selecting destabilizing mutations were identified. Molecular dynamics (MD) simulations were performed to extensively study the effect of a few mutations on NS1 structure stability and compensatory mutations. Virtual saturation mutagenesis, predicting the effect of every individual amino acid substitution on NS1 stability sequentially, revealed virtual-conserved and variable sites. The increase in number of observed and virtual-conserved regions across NS1 quaternary states suggest the role of higher order structure formation in its evolutionary conservation. Our sequence and structure analysis could enable in identifying possible protein–protein interfaces and druggable sites. Virtual screening of nearly 10,000 small molecules, including FDA-approved drugs, permitted us to recognize six drug-like molecules targeting the dimeric sites. These molecules could be promising due to their stable interactions with NS1 throughout the simulation.